Our application is in response to PA-09-174 Women's Mental Health in Pregnancy and the Postpartum Period. Approximately 10 to13 percent of women experience postpartum depression (Banti et al., 2011, Gaynes et al., 2005). Psychological interventions are efficacious for treating postpartum depression (Dennis & Hodnett, 2009); however, the prevention of postpartum depression is preferable to treatment. Research indicates that a majority of psychological interventions are not efficacious for preventing postpartum depression (Dennis & Creedy, 2008) and thus, there is a need to test new and innovative prevention strategies. Research indicates that exercise is efficacious for the treatment of depression among adults (e.g., Blumenthal et al., 2007; Mead et al, 2009) and exercise may be an ideal intervention for postpartum women who are not willing or able to use traditional treatments. For example, research indicates that a majority of breastfeeding mothers are reluctant to use antidepressants (Buist et al., 2005; Whitton et al., 1996). The purpose of this study is to examine the efficacy of exercise and wellness/support interventions for preventing postpartum depression. Specifically, 450 sedentary postpartum women (two to six weeks) with a history depression prior to pregnancy will be randomized to one of three groups: (1) telephone-based exercise intervention; (2) telephone-based wellness/support intervention; or (3) usual care. Participants will be recruited via online, email, and print advertisements. We will obtain healthcare provider consent for each participant prior to randomization. The exercise intervention will consist of a theory-based telephone intervention shown to increase exercise among postpartum women in a previous study (Lewis et al., 2011). The wellness/support condition will be on the same schedule as the exercise intervention and will address several topics related to wellness. The primary dependent variable will be depression as measured by the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and the Edinburgh Postnatal Depression Scale (EPDS). Exercise adherence will be assessed using the Seven-Day Physical Activity Recall Interview (Blair et al., 1985; Sallis et al., 1985) and the ActiGraph (i.e, an accelerometer). PUBLIC HEALTH RELEVANCE: The primary purpose of this study is to examine if exercise prevents postpartum depression, which occurs in 10 to 13 percent of women giving birth. The goal is to provide practitioners with additional strategies for preventing postpartum depression. A significant impact on postpartum depression could be made if practitioners have the ability to tell their patients to exercise as a strategy to reduce their risk for postpartum depression.